In the proposed research emphasis will be placed on in vitro binding experiments using monocrotaline, monocrotaline pyrrole and dehydroretronecine with purified macromolecules, nucleotides and enzymes. In addition, these compounds will be added to a mixed function oxidase system and their binding with microsomal protein and RNA evaluated. These experiments will be complimented by determining the ability of the pyrroles to bind to cellular macromolecules of cells in culture and in the infant animal. The anticarcinogenic effects of dehydroretronecine are being evaluated in animals having gastric carcinomas. The inhibition of cell transformation produced by DMBA with dehydroretronecine is also being studied. Preliminary data suggest the latter compound is capable of preventing transformation in cell cultures. The tumor producing ability of the pyrrolizidine alkaloids and their metabolites will be evaluated in mice using promotors to stimulate their development. In addition, non-human primates will receive repeated subcutaneous injection of dehydroretronecine in order to determine if the frequency of tumors that develop in this species is as great as that observed in rats. BIBLIOGRAPHIC REFERENCES: Allen, J.R., Hsu, I.C. and Carstens, L.A. (1975) Dehydroretronecine induced rhabdomyosarcomas in rats. Cancer Research 35, 997-1002. Allen, J.R. and Hsu, I.C. (1975) Oncogenic effects of dehydroretronecine in rats. American Journal of Pathology 78, 36a.